Recombinant DNA Advisory Committee - 10/7-8/91 
Freeman replied that only female mice were used. 
Mr. Capron expressed his agreement with Dr. Leventhal. If the theory is that the 
intraperitoneal tumor cells are killed because of the treatment but the subcutaneous 
tumor cells grow because they are not reached by the treatment, it should be an easy 
matter to perform the autopsies to verify the hypothesis. 
Dr. Wivel asked if it was known for a fact that the mouse does not have intraperitoneal 
tumor. Dr. Freeman replied that he did not know. 
Dr. Leventhal asked if statistical analysis had shown a dose-response effect. Dr. 
Freeman replied that there was evidence of a dose-response effect. 
Dr. Leventhal asked how many patients will have a chance of being cured by other 
therapies, how many animals with gross tumor have been studied, and what is the safety 
of the cell line. Dr. Freeman replied that few, if any patients, would recover with other 
therapies. Dr. Leventhal noted they had studied very few animals at day five. 
Dr. Freeman, in answer to the safety question, stated that he can easily test for 
replication competent virus in the cell line PA-1. In terms of insertional mutagenesis, 
these cells are already tumor cells, so this is not an issue. The modified tumor cells 
administered to the patients will be irradiated first. Also, the irradiated cells contain the 
TK gene which is sensitive to ganciclovir. Overall, this is a fairly safe procedure in terms 
of retrovirology. During the HGTS meeting, he described how the PA-1 cells will be 
characterized for sterility. He will ensure these test results are negative before the cells 
are administered. The cells will be tested for mycoplasma. 
Dr. Post asked if they would do any animal safety tests on the final stock of cells, that 
will be administered to the patients after irradiation. Dr. Freeman replied that they had 
performed these tests, and the animals are doing fine. Dr. McCune added that the Food 
and Drug Administration (FDA) requires these general safety tests. Both guinea pig and 
mouse standard tests will be done on the final product. 
Dr. Kelley asked for information regarding imaging, pre-treatment, and assessment of 
tumor burden. Dr. Freeman said they had decided to require laparoscopy before and 
after treatment. Tumor mass will be visualized. Hopefully, it will be possible to identify 
and mark where the mass is located to assess the effects of the therapy. This is a Phase 
I study where one looks for a dose effect. 
Dr. Mclvor said the committee should consider the generation of agents that are 
associated with the recombinant DNA process in the cell line. Helper assays must be 
performed to determine if there are other viruses generated, either from the packaging 
Recombinant DNA Research, Volume 15 
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